Mareš Pavel, Metcalf Cameron S, Baloun Jiří, Kubová Hana
Department of Developmental Epileptology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, United States of America.
PLoS One. 2025 Jan 3;20(1):e0313681. doi: 10.1371/journal.pone.0313681. eCollection 2025.
Seizures elicited by corneal 6-Hz stimulation are widely acknowledged as a model of temporal lobe seizures. Despite the intensive research in rodents, no studies hint at this model in developing animals. We focused on seven age groups of both male and female rats. Biphasic pulses with 0.3 ms duration and current intensities from 20 to 80 mA were applied transcorneally for 3 s to calculate threshold intensities for individual age groups. Threshold stimulation intensity necessary for elicitation of clonic seizures was highly age- and sex-dependent. The highest threshold was observed in the youngest (15-day-old) group then it decreased to the age of 25 days and increased again up to adulthood. The threshold current tended to be lower in females of all age groups. The incidence of convulsive seizures increased with stimulation intensity up to postnatal day 25 in either sex. In rats of 31 days old and older convulsions occurred irregularly regardless of the stimulation current and sex. For subsequent analysis, the animals were categorized into two groups: juveniles, aged 15 to 25 days, and adolescents/adults, aged 31 days and older. Our statistical analyses revealed an increased risk of convulsions after the stimulation with higher intensities in juvenile but not adolescent/adult rats. Females tended to be more sensitive to the stimulation with lower currents than males. Seizure severity was higher in females 18- to 25-day old compared to males of the same age and the seizure duration increased with stimulation intensities in juvenile but not adolescent/adult animals. The data extend the use of the rat 6 Hz model to immature animals and may be useful as a model of pediatric temporal lobe seizures.
角膜6赫兹刺激诱发的癫痫发作被广泛认为是颞叶癫痫的一种模型。尽管对啮齿动物进行了深入研究，但尚未有研究提示该模型在发育中的动物身上的情况。我们聚焦于七个年龄组的雄性和雌性大鼠。将持续时间为0.3毫秒、电流强度从20毫安到80毫安的双相脉冲经角膜施加3秒，以计算各个年龄组的阈值强度。诱发阵挛性癫痫发作所需的阈值刺激强度高度依赖年龄和性别。在最年幼（15日龄）的组中观察到最高阈值，然后在25日龄时下降，到成年期又再次升高。所有年龄组的雌性阈值电流往往较低。惊厥性癫痫发作的发生率随刺激强度增加，直至出生后第25天，无论性别如何。在31日龄及以上的大鼠中，惊厥发作不规则，与刺激电流和性别无关。为了后续分析，将动物分为两组：15至25日龄的幼年期和31日龄及以上的青少年期/成年期。我们的统计分析显示，幼年期大鼠在高强度刺激后惊厥风险增加，而青少年期/成年期大鼠则不然。雌性往往比雄性对较低电流的刺激更敏感。18至25日龄的雌性大鼠癫痫发作严重程度高于同龄雄性，且癫痫发作持续时间在幼年期动物中随刺激强度增加，而在青少年期/成年期动物中则不然。这些数据将大鼠6赫兹模型的应用扩展到未成熟动物，可能作为小儿颞叶癫痫的一种模型。
